Description:
E 2012 is a potent γ-secretase modulator.
In the present study, 9 dogs were treated with a single dose of the γ-secretase modulator E2012, the γ-secretase inhibitor
LY450139, or vehicle with a dosing interval of 1 week. The isoform Aβ(1-37) was significantly increased in a dose-dependent
manner in response to treatment with E2012, while Aβ(1-39), Aβ(1-40) and A(1-42) decreased.
E2012, a gamma secretase modulator without affecting Notch processing, aimed at Alzheimer's disease by reduction of amyloid
β-42, induced cataract following repeated doses in the rat.E2012 inhibits 3β-hydroxysterol Δ24-reductase (DHCR24) at the final
step in the cholesterol biosynthesis. In vivo lenticular concentration of E2012 after 13-week repeated dose with cataract was well
above those where inhibition was observed in vitro.E2012 induces cataract in the rat by inhibiting DHCR24 at the final step of
cholesterol synthesis with associated elevation in desmosterol within the lens, preceded by desmosterol changes that would serve
as a predictive safety biomarker for lenticular opacity.

Chemical Information
Catalog

DC8277

Purity of current batch:

>98%

Molecular Weight (MW)

419.49

Molecular Formula

C25H26FN3O2

CAS No.

870843-42-8

Solubility (25°C)

DMSO

Storage

Store at -20°C (desiccating conditions).

Handling:
Providing storage is as stated on the product vial and the vial is kept tightly sealed, the product can be stored for up to 24 months.
Wherever possible, you should prepare and use solutions on the same day. However, if you need to make up stock solutions in
advance, we recommend that you store the solution as aliquots in tightly sealed vials at -20°C. Generally, these will be useable
for up to one month. Before use, and prior to opening the vial we recommend that you allow your product to equilibrate to room
temperature for at least 1 hour.